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The microtubule-associated protein tau is implicated in the formation of oligomers and fibrillar aggregates that evade proteostasis control and spread from cell-to-cell. Tau pathology is accompanied by sustained neuroinflammation and, while the release of alarmin mediators aggravates disease at late stages, early inflammatory responses encompass protective functions. This is the case of the Ca2+-binding S100B protein, an astrocytic alarmin which is augmented in AD and which has been recently implicated as a proteostasis regulator, acting over amyloid β aggregation. Here we report the activity of S100B as a suppressor of tau aggregation and seeding, operating at sub-stoichiometric conditions. We show that S100B interacts with tau in living cells even in microtubule-destabilizing conditions. Structural analysis revealed that tau undergoes dynamic interactions with S100B, in a Ca2+-dependent manner, notably with the aggregation prone repeat segments at the microtubule binding regions. This interaction involves contacts of tau with a cleft formed at the interface of the S100B dimer. Kinetic and mechanistic analysis revealed that S100B inhibits the aggregation of both full-length tau and of the microtubule binding domain, and that this proceeds through effects over primary and secondary nucleation, as confirmed by seeding assays and direct observation of S100B binding to tau oligomers and fibrils. In agreement with a role as an extracellular chaperone and its accumulation near tau positive inclusions, we show that S100B blocks proteopathic tau seeding. Together, our findings establish tau as a client of the S100B chaperone, providing evidence for neuro-protective functions of this inflammatory mediator across different tauopathies., The calcium binding protein S100B is an abundantly expressed protein in the brain and has neuro-protective functions by inhibiting Aβ aggregation and metal ion toxicity. Here, the authors combine cell biology and biochemical experiments with chemical kinetics and NMR measurements and show that S100B protein is an extracellular Tau chaperone and further characterize the interactions between S100B and Tau.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder commonly diagnosed in infants and characterized by progressive cerebellar ataxia, spasticity, motor sensory neuropathy and axonal demyelination. ARSACS is caused by mutations in the SACS gene that lead to truncated or defective forms of the 520 kDa multidomain protein, sacsin. Sacsin function is exclusively studied on neuronal cells, where it regulates mitochondrial network organization and facilitates the normal polymerization of neuronal intermediate filaments (i.e., neurofilaments and vimentin). Here, we show that sacsin is also highly expressed in astrocytes, C6 rat glioma cells and N9 mouse microglia. Sacsin knockout in C6 cells (C6Sacs−/−) induced the accumulation of the glial intermediate filaments glial fibrillary acidic protein (GFAP), nestin and vimentin in the juxtanuclear area, and a concomitant depletion of mitochondria. C6Sacs−/− cells showed impaired responses to oxidative challenges (Rotenone) and inflammatory stimuli (Interleukin-6). GFAP aggregation is also associated with other neurodegenerative conditions diagnosed in infants, such as Alexander disease or Giant Axonal Neuropathy. Our results, and the similarities between these disorders, reinforce the possible connection between ARSACS and intermediate filament-associated diseases and point to a potential role of glia in ARSACS pathology.

A new, efficient, green, endogenous water-triggered, solvent- and catalyst-free ultrasound-assisted one-pot Groebke–Blackburn–Bienayme reaction/SNAr/ring-chain azido-tautomerization strategy to synthesize bound-type fused bis-heterocycles imidazo or benzo[d]imidazo[2,1-b]thiazoles and 1,5-disubstituted tetrazole (1,5-DsT) containing quinoline moiety is described, which allows synthesis of two types of fused heterocycles in one step under mild green conditions. Antibacterial and antiamebic activities of selected newly synthesized compounds were carried out against three bacterial species: Gram-positive bacterium Staphylococcus aureus ATCC 6538 and Gram-negative bacteria Pseudomonas aeruginosa ATCC 13384 and Escherichia coli O55 and against one amebic species: Entamoeba histolytica.

Introduction Cell therapy in regenerative endodontics introduces an alternative option to classic treatment strategies for complex endodontic cases. The aim of this case report was to describe cell-based therapy using allogeneic umbilical cord mesenchymal stem cells (UC-MSCs) encapsulated in a bioscaffold for a complex case of a mature permanent tooth with apical periodontitis and accidental root perforation. Methods A healthy 19-year-old man undergoing orthodontic treatment was referred for endodontic treatment in tooth #7; he was diagnosed with apical periodontitis during a previously initiated treatment associated with accidental perforation of the radicular cervical third. The root perforation was sealed with glass ionomer and composite resin, and the root canal was instrumented, disinfected, and dressed with calcium hydroxide. After 3 weeks, allogeneic UC-MSCs were encapsulated in platelet-poor plasma and then implanted into the root canal, and Biodentine (Septodont, Saint-Maur-des-Fosses, France) was placed below the cementoenamel junction. Finally, the tooth was restored with composite resin. Results Follow-up examinations were performed 6 months and 1 year later. The examinations included periapical radiography, cone-beam computed tomographic imaging, and sensitivity and vitality tests. Radiographic and cone-beam computed tomographic images indicated remission of the apical lesion. Clinical evaluations revealed normal responses to percussion and palpation tests; the tooth was responsive to the electric pulp test, and the vitality test indicated low blood perfusion units. Conclusions This case report reveals the potential use of allogeneic cellular therapy using encapsulated UC-MSCS in a platelet-poor plasma scaffold for a complex case of a permanent tooth with apical periodontitis and root perforation.

A series of 18 3-tetrazolyl-tetrazolo[1,5-a]quinolines were synthesized in 21–90% yields via a novel one-pot Ugi-azide/SNAr/ring–chain azido-tautomerization process. We report also the synthesis of 10 3-imidazo[1,2-a]pyridin-tetrazolo[1,5-a]quinolines in 28–94% yields via a novel one-pot Groebke–Blackburn–Bienayme/SNAr/ring–chain azido-tautomerization process. Both synthetic strategies involve the use of microwaves or ultrasound, and catalyst-free conditions. Finally, we show the synthesis of the tetrazolo[1,5-a]quinoline-3-carbaldehyde and tetrazolo[1,5-a]quinoline-3-dimethyl acetal at room temperature in methanol as solvent.